Preparation of trifluoromethylphenyl nitrophenylethers

ABSTRACT

A process for preparing trifluoromethylphenyl nitro phenylethers which comprises treating a trifluoromethylhalobenzene with a base in a cosolvent system to afford a trifluoromethyl phenolate which may be isolated as its free phenol or reacted with an appropriately substituted halobenzene to afford a diphenylether herbicide or a precursor thereto.

This is a division of application Ser. No. 071,341 filed May 1, 1979.

BACKGROUND OF THE INVENTION

This invention relates to a process for preparing known active nitro,trifluoromethyl containing diphenylether herbicides having the formula:##STR1## wherein X is hydrogen, halo such as chloro, bromo, fluoro andthe like; trihalo lower alkyl such as trifluoromethyl and the like;lower alkyl such as methyl, ethyl, propyl, iso-propyl, n-butyl,sec-butyl, tert-butyl, and the like, X' is selected from hydrogen, halo,such as chloro, bromo, fluoro and the like, cyano, lower alkyl such asmethyl, ethyl, n-propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl andthe like; lower alkoxy such as methoxy, ethoxy, iso-propoxy, butoxy,pentoxy and the like; carboxy; carbalkoxy such as carbomethoxy,carboethoxy, carbo-iso-propoxy, carbo-tert-butoxy, carbo-n-pentoxy, andthe like; carbalkoxyalkoxy such as 1-carboethoxyethoxy,1-carbomethoxypropoxy and the like; carbamoyl; mono- and di-lower alkylsubstituted carbamoyl such as N-methylcarbamoyl, N-iso-propylcarbamoyl,N-n-butylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl and thelike; substituted alkoxycarbonyl such as 2-methoxyethoxycarbonyl,2-ethoxypropoxycarbonyl, 2-iso-butoxyethylcarbonyl and the like;alkenyloxycarbonyl such as 2-propenyloxycarbonyl,2-(2-methylpropenyloxy)carbonyl and the like; or trifluoromethyl and X"is halo or trifluoromethyl with the proviso that when X" is halo X istrifluoromethyl.

The following U.S. patents disclose trifluoromethyl substituteddiphenylethers U.S. Pat. Nos.: 3,798,276; 3,928,416; 4,031,131;4,063,929; 3,784,635; 4,087,272; 4,002,662; 4,001,005; 3,983,168;3,979,437; 3,941,830; 3,907,866; 3,873,302; 3,954,829; 3,839,444;3,957,865; 4,017,300, and 3,862,209.

A key intermediate in the synthesis of the diphenyl ether (I, supra) isthe substituted or unsubstituted trifluoromethylphenol. There arevarious routes to this compound. See for example U.S. Pat. Nos.3,888,932; 3,772,344; 3,819,755 and references cited therein. Thepresent processes either involve too many steps or are economicallyunattractive or both. [See Mooradian, et al., J. Am. Chem. Soc., 73,3470-2 (1951; McBee et al., J. Am. Chem. Soc., 73, 1325-6 (1951); Jones,R. G., J. Am. Chem. Soc., 69, 2346-50 (1947); and Lavagnino, E. R., etal., Org. Preparations and Procedures International, Vol. 9, pps 96-98(1977).]

The basic problem in the preparation of a trifluoromethyl phenol is thesensitivity of the trifluoromethyl radical to not only concentrated buteven dilute base. (See Jones, R. G., J. American Chemical Society, 69,2346-50 (1947)).

It has now been discovered that by employing a special solvent system toregulate the amount of base in solution and reduce the presence ofwater, trifluoromethylphenates can be produced in a single step in goodyield, in situ. The corresponding trifluoromethylphenols can be isolatedupon acidification, or condensed directly with appropriately substitutedhalo nitrobenzenes to afford herbicidal diphenyl ethers or precursorsthereof.

The following equation illustrates this process for preparingtrifluoromethylphenol from a chloro substituted compound however, it isto understood that in place of the chloro radical, a fluoro radicalcould also be used; ##STR2## wherein X is as defined above and M is acation derived preferentially from an alkali metal or alternatively froman alkaline earth metal. Hydroxides such as sodium hydroxide, potassiumhydroxide, calcium hydroxide, magnesium hydroxide, and the like may beemployed with sodium being a preferred cation and potassium the mostpreferred cation. The reaction is conducted at a temperature in therange of from about 50° to about 100° C. and, preferably, in the rangeof from about 65° to about 85° C. for a period of time preferably in therange of from 5 hours to 5.5 days and most preferably in the range offrom 10 to 55 hours. It is understood that some product is formed withinseveral hours, however, the time periods set forth above represent theoptimum time periods. The reaction is generally conducted at atmosphericpressure. Other halobenzenes (III, supra) include ##STR3## wherein X andX" are as defined above and X² is fluro or chloro.

A key element in this invention is the cosolvent system which isprepared from a dipolar, aprotic solvent and a non-nucleophilic,hydroxylated cosolvent.

Dipolar, aprotic solvents employed in this invention include solventshaving dielectric constants in the range of from about 30 to about 70which solvents are inert or substantially inert to the base employed.Examples of the preferred dipolar, aprotic solvents include dimethylsulfoxide, tetrahydrothiophene-1,1-dioxide, hexamethylphosphorictriamide and the like.

The non-nucleophilic, hydroxylated cosolvent which provides forincreased solubility of the metal hydroxide is believed to impartstability by hydrogen bonding with the formed 4-trifluoromethylphenolatesalt.

Non-hindered alcohol such as methanol, ethanol, n-propanol oriso-propanol, however, may enter into competitive reactions with the4-trifluoromethylphenolate resulting in formation of undesiredby-products. Less nucleophilic n-alcohols (C₄ and above) are moredesirable as cosolvents than the C₁ -C₃ alcohols, listed above.

The hydroxylated cosolvents employed in this invention are those havingthe following structural formla: ##STR4## wherein R, R¹, R², R³, R⁴, R⁵,R⁶ and R⁷ are the same or different groups selected from hydrogen;straight or branched lower alkyl, substituted or unsubstituted phenylwherein the phenyl substituents may be alkyl, halo, lower alkoxy, orbenzyl, and the like; R⁸ is lower alkyl; n and n² are 0 or 1; n¹ is 0 to2, n³ is an integer of from 1 to 10; n⁴ is 2 to 4 provided that n¹ is 2only when n and n² are both 0, otherwise the sum of n¹ and n² may not begreater than 1; when n³ is greater than 2, the sum of n and n² may notsimultaneously be greater than 1 and n¹ must be 0; when R⁷ is hydrogen,n¹ must be zero and the sum of n and n² must be 1 such that at least 3of the groups R, R' plus either the pair R² and R³ or the pair R⁵ and R⁶must not be hydrogen.

Examples of the hydroxylated solvents include tert-butyl alcohol,pinacol, pentaerythritol, 2,4-dimethyl-2,4-pentanediol,2,4-dimethyl-2,3,4-pentanetriol, 2,4-dimethyl-1,2-pentanediol,2,4-dimethyl-3-pentanol, 2,2,4-trimethyl-3-pentanol,2,2-dimethyl-1-propanol, ##STR5## 1-methyl-1-cyclohexanol,2-iso-propyl-1-cyclopentanol and the like.

The cosolvents are employed at a ratio in the range of from about 1 toabout 30 parts of the non-nucleophilic hydroxylated cosolvent to about100 parts of the dipolar, aprotic solvent and preferably at a ratio inthe range of from about 5 to about 20 parts of the non-nucleophilicsolvent to about 100 parts of the dipolar, aprotic solvent.

The free phenol (II, below) may be isolated by treatment with acid ormay be reacted with an appropriately substituted halobenzene to affordeither a diphenyl ether herbicide or precursor which may be reactedfurther to afford the desired diphenyl ether (I, supra).

This procedure is illustrated by the following: ##STR6## wherein M, X,X' and X" are as defined above and halo is preferably chloro or fluoro.Fluoro is preferred for enhancing reaction rates while chloro ispreferred in terms of lower raw material costs.

The following illustrates in greater detail the preparation of thepreferred diphenyl ether herbicides however, it is to be understood thatother products falling within the generic description (I, supra) mayalso be prepared in a similar manner: ##STR7## wherein X, X' and M areas defined above. Especially preferred are those compounds where X ishydrogen or chloro and X¹ is lower alkyl, lower alkenyl, or loweralkoxyalkyl esters or alkyl or dialkyl amides thereof. The lower alkylesters can be readily hydrolyzed under acidic or basic conditions toafford the carboxylic acid which can readily be converted to alkali oralkaline earth metal salts or to various amine salts as desired.

The reaction between the trifluoromethylphenolate (II supra) and thehalonitrobenzene (IV, supra) is generally conducted at a temperature inthe range of from about 25° to 130° C. and preferably in the range offrom about 25°-85° C. when the halo is fluoro and 60°-130° C.,preferably 65°-85° C., when the halo is chloro. Dipolar, aproticsolvents which may be employed include dimethylsulfoxide,dimethylformamide, tetrahydrothiophene 1,1-dioxide, hexamethylphosphorictriamide, N-methylacetamide, ethylene carbonate, dimethoxy ethane,1,4-dioxane and the like. Non-nucleophilic, hydroxylated cosolventsdescribed above may advantageously be employed at 1-10 parts per 100parts of the dipolar, aprotic solvent. If the free phenols (IIa or IId)are employed, the reaction must be conducted in the presence of analkali metal or alkaline earth metal base such as anhydrous hydroxides,carbonates, bicarbonates and the like; preferred alkali metals arepotassium and sodium.

Synthesis of 5-chloro-2-nitrobenzoates (i.e., X is carboxy) aredescribed in Beilstein, IX, p. 401 and may be represented as follows:##STR8## wherein R¹ is hydrogen or lower alkyl.

The synthesis of 5-fluoro-2-nitrobenzoic acid from 3-fluorobenzoic acidhas been described by J. H. Slothouwer, Rec. trav. chim., 33, 324-42,1914.

The following examples illustrate the process of this invention but arenot intended to limit the invention in any manner.

EXAMPLE 1 2-Chloro-4-trifluoromethylphenol and potassium salt

To a flask equipped with a stirrer, thermometer, condenser and dryingtube is added 3,4-dichlorobenzotrifluoride (21.5 g, 0.10 mole),potassium hydroxide pellets (85%, 0.20 mole) and dimethyl sulfoxide (100ml). The reaction mixture is warmed to 65° C. for five hours duringwhich time little reaction occurred. Tert-butyl alcohol (10 ml) is thenadded and the heating continued at 65° C. over the weekend. The reactionmixture is cooled, poured slowly onto ice (400 g), and extracted withtoluene (100 ml, then 25 ml) to remove any unreacted starting material.To the yellow aqueous layer containing 2-chloro-4-trifluoromethylphenol,potassium salt (still cold) is added carbon tetrachloride (100 ml). Themixture is then acidified rapidly (pH 1) with conc. hydrochloric acid.The carbon tetrachloride layer is decanted, dried with anhydrous sodiumsulfate and reduced under vacuum to afford 13.5 g of2-chloro-4-trifluoromethylphenol Distillation at 3.0 mm, affords 10.8 g(69% yield) of substantially pure material, bp 79.5°-80.5° C. ElementalAnal. Calcd. for C₇ H₄ ClF₃ O: C, 42.75; H, 2.06; Cl, 18.04; F, 29.00;Found: C, 43.01; H, 2.24; Cl, 17.28; F, 28.52.

EXAMPLE 2 2-Chloro-4-trifluoromethylphenol and potassium salt

To a flask equipped with a stirrer, thermometer, condenser and dryingtube is added dimethyl sulfoxide (100 ml), powdered potassium hydroxidepellets (85%, 0.38 mole), 3,4-dichlorobenzotrifluoride (21.5 g, 0.10mole) and pinacol (10 g). The reaction mixture is warmed at 75° C. for52 hours, cooled and an aliquot analyzed by GLC to be 95% completecompared to unreacted 3,4-dichlorobenzotrifluoride. The product IIa(X=Cl) was isolated and used directly in Example 9B.

Variations of Example 1 used in the preparation of2-chloro-4-trifluoromethylphenol are illlustrated in Table I:

                                      TABLE I                                     __________________________________________________________________________     ##STR10##                                                                               Non-Nucleo-                                                                            Dipolar,                                                        Alkali                                                                             philic   Aprotic                                                   Ex Moles                                                                            Metal                                                                              Cosolvent                                                                              Solvent                                                                            Time                                                                             Temp.                                                                             Yield                                         No.                                                                              of III                                                                           (Moles)                                                                            (ml)     (ml) (hrs)                                                                            °C.                                                                        (%)                                           __________________________________________________________________________    3  0.1                                                                              KOH (0.2)                                                                           ##STR11##                                                                             DMSO (100)                                                                         65 65  69                                            4  0.1                                                                              KOH (0.48)                                                                          ##STR12##                                                                             DMSO (100)                                                                         132                                                                              65-75                                                                             73                                            5  0.1                                                                              KOH  tert-butanol                                                                           DMSO 47 62-75                                                                             90                                                  (0.45)                                                                             (20)     (100)                                                     6  2.5                                                                              KOH (8.76)                                                                          ##STR13##                                                                             DMSO (2500)                                                                        34 69-74                                                                             80                                            7  0.1                                                                              KOH   --      DMSO 5  65  0                                                   (0.2)         (100 ml)                                                  __________________________________________________________________________

By following the general procedures of Examples 1 and2,4-trifluoromethylphenol can generally be prepared from 4-chloro- or4-fluorobenzotrifluoride. In addition, 2-trifluoromethylphenols can beprepared following the general procedures described in Examples 1 and 2,but employing 2-halo, halo being florine or chlorine, benzotrifluorides,a non-limiting example of which follows:

EXAMPLE 8 4-Chloro-2-trifluoromethylphenol

To a 300 ml, 3-necked flask fitted with a stirrer, condenser,thermometer and drying tube is added dimethylsulfoxide (100 ml),tert-butanol (20 ml), powdered potassium hydroxide (KOH) pellets (85%,30 g) and 2,5-dichlorobenzotrifluoride (21.5 g, 0.10 mole). The reactionmixture is warmed to 71°-73° C. for 60 hours, then additional KOH (10 g)is added and heating is continued at 73°-75° C. for 24 hours. Thereaction mixture is cooled and the solvent partially removed bydistillation at 0.9 mm, bp 55° C.). The cooled pot residue is thenpoured into ice water (1000 g) which had been preacidified to pH 1 withconc. HCl (50 ml). The aqueous mixture is extracted with carbontetrachloride (CCl₄), the CCl₄ layer decanted and dried and the solventremoved under vacuum to afford 10.8 g of4-chloro-2-trifluoromethylphenol, which is sublimed to afford pureproduct, mp 81°-81.5° C. Elemental Anal. Calcd for C₇ H₄ ClF₃ O: C,42.75; H, 2.06; Cl, 18.04: Found: C, 42.54; H, 2.36; Cl, 18.16.##STR14##

EXAMPLE 1A Methyl 5-Chloro-2-nitrobenzoate

5-Chloro-2-nitrobenzoic acid (20.1 g,; 0.10 mol), is dissolved inanhydrous methanol (100 ml) and anhydrous hydrogen chloride gas isbubbled into the reaction mixture for 4 hours at room temperature. Thereaction mixture is then poured into water and the aqueous mixturetriturated with hexane, the hexane layer decanted, dried (anhd. MgSO₄)and the solvent removed under vacuum to afford 11.7 g of methyl5-chloro-2-nitrobenzoate, mp 50°-51° C.

EXAMPLE 2A Methyl 3-Fluorobenzoate

To a solution of anhydrous hydrochloric acid (10.5 g) in anhydrousmethanol (100 ml) is added m-fluorobenzoic acid (13.3 g.; 0.095 mole).The reaction mixture is stirred at room temperature overnight. Thesolvent and anhydrous hydrochloric acid are then removed under vacuumand the residue slurried with hexane (100 ml). The hexane insolublelayer is decanted and the hexane solution water washed (2×100 ml) beforedrying with anhydrous magnesium sulfate. The hexane filtrate is thenconcentrated under vacuum to afford 11.0 g (75% yield) of methyl3-fluorobenzoate as a yellow liquid. Elemental anal. calcd. for C₈ H₇FO₂ : C, 62.35; H, 4.57; F, 12.33. Found: C, 62.52; H, 4.70; F, 11.89.

EXAMPLE 3A Methyl 3-Fluorobenzoate

To a 1-liter flask fitted with a stirrer, addition funnel, condenser,and drying tube containing diethyl ether (200 ml) and methanol (anhd.;64 g,; 2.0 moles] is added dropwise m-fluorobenzoyl chloride (317 g,;2.0 moles) at room temperature over a 3 hour period. Additional methanol(10 ml) is added and the reaction mixture is stirred at room temperatureovernight. The reaction mixture is then filtered through a bed ofsilicic acid and the solvent removed under vacuum to afford 285 grams ofmethyl 3-fluorobenzoate (92.5% yield). This was identical to the productprepared in Example 2A.

By following substantially the procedure of Example 3A and bysubstituting for the methanol recited therein an equimolar quantitiy ofanother alcohol there may be obtained other desired esters. Thefollowing Table II taken together with the flow diagram illustrates thisprocess:

                  TABLE II                                                        ______________________________________                                         ##STR15##                                                                                    ##STR16##                                                     Ex                 Molecular                                                  No.   R.sup.10     Formula    Elemental Analysis                              ______________________________________                                        4A   C.sub.2 H.sub.5                                                                             C.sub.9 H.sub.9 FO.sub.2                                                                  --                                             5A   CH.sub.2 CH.sub.2 N(CH.sub.3).sub.2                                                         C.sub.11 H.sub.14 FNO.sub.2                                                              Calcd:                                                                              C,  62.50;                                                                    H,  6.70;                                                                     F,  9.00;                                                               Found:                                                                              C,  62.25;                                                                    H,  6.76;                                                                     F,  8.48;                                 6A   C.sub.8 H.sub.17                                                                            C.sub.15 H.sub.21 FO.sub.2                                                               Calcd:                                                                              C,  71.40;                                                                    H,  8.38;                                                                     F,  7.52;                                                               Found:                                                                              C,  71.45;                                                                    H,  8.57;                                                                     F,  7.37;                                 7A                                                                                  ##STR17##    C.sub.10 H.sub.10 FO.sub.2                                                               Calcd:                                                                              C, H, F,                                                                          66.25; 5.57;  10.50;                                                Found:                                                                              C,  65.88;                                                                    H,  5.79;                                                                     F,  10.13;                                8A   CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.3                                                         C.sub.11 H.sub.13 FO.sub.2                                                               --                                              9A   CH.sub.2 CH.sub.2 OH                                                                        C.sub.9 H.sub.9 FO.sub.3                                                                 --                                              10A  CH.sub.2 CH.sub.2 CH.sub.3                                                                  C.sub.10 H.sub.11 FO.sub.2                                                               --                                              11A  CH.sub.2 CH.sub.2 OCH.sub.3                                                                 C.sub.10 H.sub.11 FO.sub.3                                                               --                                              ______________________________________                                    

EXAMPLE 12A N,N-Diethyl-3-fluorobenzamide

To a 50 ml flask fitted with a stirrer, condenser, drying tube and anaddition funnel is added m-fluorobenzoyl chloride (15.9 g, 0.10 mole)and benzene (100 ml). Then a solution of diethylamine (14.6 g, 0.20mole) in benzene (100 ml) is added dropwise over 1 hour and the reactionmixture allowed to stir at room temperature overnight. Water (150 ml) isthen added rapidly and after trituration for a few minutes, the benzenelayer is decanted and washed repeatedly with water (5×150 ml), dried(anhyd. Na₂ SO₄) and the solvent removed under vacuum to afford 18 gramsof N,N-diethyl-3-fluorobenzamide as a yellow oil. Elemental analysiscalculated for C₁₁ H₁₄ FNO: C, 67.70; H, 7.22; F, 9.72; N, 7.16; Found:C, 66.40; H, 7.08; F, 9.65; N, 6.92

EXAMPLE 13A 3-Fluorobenzamide

Into a stirred solution of m-fluorobenzoyl chloride (15.9 g, 0.10 mole)in benzene (200 ml) at 5° C. is bubbled anhydrous ammonia gas for 30minutes. A white solid precipitates and the reaction mixture is allowedto stir at room temperature overnight. The white solid is removed byfiltration and then triturated with water. The solid is dried to afford10 g of m-fluoroenzamide, mp 130°-33° C. Elemental analysis calculated.for C₇ H₆ FNO: C, 60.40; H, 4.34; F, 13.66; N, 10.08. Found: C, 59.97;H, 4.43; F, 13.86; N, 10.39.

5-Fluoro-2-Nitrobenzoate Esters and Amides

By a modification of the method of Slothouwer, (supra) in which isdescribed the preparation of 5-fluoro-2-nitrobenzoic by nitration of3-fluorobenzoic acid, under standard nitration conditions the3-fluorobenzoate esters and benzamides were nitrated as follows:

EXAMPLE 14A Methyl 5-Fluoro-2-nitrobenzoate

To a 500 ml, 4-necked flask fitted with a stirrer, thermometer, additionfunnel and reflux condenser is charged sulfuric acid (50 ml) and methylm-fluorobenzoate (8.5 g, 0.055 mole). The reaction mixture is thencooled to 5° C. and a solution of potassium nitrate (reagent 5.57 g,0.055 mole) is concentrated sulfuric acid (50 ml) is added dropwise overa 30 minute period. Ten minutes after completion of addition thereaction mixture is poured onto 500 g of cracked ice and the productextracted into benzene (3×100 ml). The combined benzene extracts aredried with anhydrous magnesium sulfate and the filtrate reduced in vacuoto give 10.6 g (96%) of product, which is a yellow liquid. Anal. Calcd.for C₈ H₆ FNO₄ : C, 48.20; H, 3.04; F, 9.54; N, 7.02. Found: C, 50.15;H, 3.34; F, 9.17; N, 6.77.

By following substantially the procedure of Example 14A and bysubstituting an appropriate ester or amide of 3-fluorobenzoic acid forthe ester recited therein the products depicted in Table III may beprepared.

                  TABLE III                                                       ______________________________________                                         ##STR18##                                                                    Ex                 Molecular                                                  No.   R.sup.11     Formula    Elemental Analysis                              ______________________________________                                        15A  OH            C.sub.7 H.sub.4 NO.sub.4                                                                 Calcd:                                                                              C,  45.40;                                                                    H,  2.18;                                                                     F,  10.25;                                                              Found:                                                                              C,  45.02;                                                                    H,  2.13;                                                                     F,  9.84;                                 16A  OC.sub.2 H.sub.5                                                                            C.sub.9 H.sub.8 FNO.sub.4                                                                --                                              17A  OC.sub.8 H.sub.17                                                                           C.sub.15 H.sub.20 FO.sub.4                                                               Calcd:                                                                              C,  60.60;                                                                    H,  6.78;                                                                     F,  6.40;                                                               Found:                                                                              C,  63.10;                                                                    H,  7.08;                                                                     F,  6.50;                                 18A  N(C.sub.2 H.sub.5).sub.2                                                                    C.sub.11 H.sub.13 FN.sub.2 O.sub.3                                                       Calcd:                                                                              C,  55.00;                                                                    H,  5.45;                                                                     F,  7.90;                                                               Found:                                                                              C,  54.89;                                                                    H,  5.46;                                                                     F,  7.82;                                 19A                                                                                 ##STR19##    C.sub.10 H.sub.9 FNO.sub.4                                                               --                                              20A  NH.sub.2      C.sub.7 H.sub.5 FN.sub.2 O.sub.3                                                         --                                              21A  O(CH.sub.2).sub.3 CH.sub.3                                                                  C.sub. 11 H.sub.12 NO.sub.4                                                              --                                              22A  OCH.sub.2 CH.sub.2 CH.sub.3                                                                 C.sub.10 H.sub.10 FNO.sub.4                                                              Calcd:                                                                              C,  52.86;                                                                    H,  4.43;                                                                     F,  6.16;                                                               Found:                                                                              C,  53.34;                                                                    H,  4.40;                                                                     F,  5.97;                                 23A  OCH.sub.2 CH.sub.2 OCH.sub.3                                                                C.sub.10 H.sub.10 FNO.sub.5                                                              Calcd:                                                                              C,  49.58;                                                                    H,  4.14;                                                                     F,  5.75;                                                               Found:                                                                              C,  49.57;                                                                    H,  4.00;                                                                     F,  5.85;                                 24A  OCH.sub.2 CH.sub.2 OH                                                                       C.sub.9 H.sub.8 FNO.sub.5                                                                Calcd:                                                                              C,  47.37;                                                                    H,  3.53;                                                                     F,  7.91;                                                               Found:                                                                              C,  47.53;                                                                    H,  3.74;                                                                     F,  7.73;                                 ______________________________________                                    

EXAMPLE 25A Ethyl 2-(5-Fluoro-2-nitrophenoxy)propionate

2,4-Difluoronitrobenzene (16.9 g; 0.10 mole), ethyl lactate (11.8 g;0.10 mole), and anhydrous potassium carbonate (13.8 g, 0.10 mole) arecombined in dioxane (200 ml) and the temperature is brought to 95° C.over a 1.5 hour period and maintained at 95° C. for 3 hours. Thereaction mixture is cooled to room temperature, the inorganic solidsremoved by filtration and the solvent removed under vacuum to afford adark colored oil, from which low boiling fractions are removed bydistillation (bp., 79° C./0.5 mm). The pot residue is then cooled toafford 15.9 g of crude product, which is recrystallized fromligroin/acetone to afford ethyl 2-(5-fluoro-2-nitrophenoxy)propionate asyellow needles, m.p. 64°-65° C. Elemental anal. Calcd for C₁₁ H₁₂ FNO₅ :C, 51.4; H, 4.70; F, 7.38; N, 5.45. Found: C, 51.35; H, 4.74; F, 7.60;N, 5.44.

EXAMPLE 26A 2-Ethoxy-4-fluoronitrobenzene

To a solution of anhydrous sodium ethoxide (0.55 mole) [prepared bydissolving sodium metal (12.6 g, 0.55 mole) in anhydrous ethanol (300ml)] at 0° C. is added 2,4-difluoronitrobenzene (79.5 g, 0.50 mole)dropwise over an 8 hour period. Upon completion of addition the reactionmixture is allowed to warm to room temperature and stirred overnight.The solid is removed by filtration, and triturated with toluene andwater. The toluene extract is combined with the original filtrate, driedwith anhydrous sodium sulfate and the solvent is removed under vacuum toafford 218 g of a yellow oil which was distilled at 0.3 mm, b.p. 95°-98°C. to afford substantially pure 2-ethoxy-4-fluoronitrobenzene. ##STR20##

EXAMPLE 1B Methyl 5(2-chloro-4-trifluoromethylphenoxy)2-nitrobenzoate

To a 5-liter, 4-necked flask fitted with a stirrer, thermometer,addition funnel, reflux condenser and drying tube is added dimethylsulfoxide (200 ml), 2-chloro-4-trifluoromethylphenol) (715 g, 3.64mole), and anhydrous potassium carbonate (520 g, 3.72 moles). Thereaction mixture is stirred at room temperature overnight under anitrogen atmosphere. Then methyl 5-fluoro-2-nitrobenzoate (724 g, 3.64moles) is added over a 1 hour period (slight exotherm to 31° C.). Afterstirring overnight at room temperature, the inorganic solids are removedby filtration and 1700 ml of dimethyl sulfoxide removed under vacuum (1mm, pot temp. of 85° C., vapor temp. of -40° C.). The residue is dilutedwith a large volume of carbon tetrachloride and water washed. Theorganic layer is dried with anhydrous magnesium sulfate and the solventremoved under vacuum to afford 1142 g of methyl5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate (84% yield). Anal.Calcd. for C₁₅ H₉ ClF₃ NO₅ : C, 47.90; H, 2.42; Cl, 9.45; F, 15.20; N,3.73. Found: C, 47.83; H, 2.47; Cl, 9.15; L F, 14.84; N, 3.69.

By following the procedure of Example 1B and by varying temperature,time and solvent a repeat was made of the methyl ester. Also preparedwas the ethyl ester and several other esters. The following Table IVillustrates this process.

                                      TABLE IV                                    __________________________________________________________________________     ##STR21##                                                                    __________________________________________________________________________    Example             Time  Temp      Yield                                     No.    R.sup.11     (hours)                                                                             (°C.)                                                                       Solvent                                                                            (%)                                       __________________________________________________________________________    2B     OH           8     70-100                                                                             DMSO 1                                         3B     OCH.sub.3    1     70   DMSO 30                                        4B     OCH.sub.3    8     reflux                                                                             dioxane                                                                            10                                        5B     OCH.sub.3    48    25   DMSO 87                                        6B     OCH.sub.3    5     25   DMSO 84                                        7B     OCH.sub.3    8     25-48                                                                              DMSO 77                                        8B     OC.sub.2 H.sub.5                                                                           24    25   DMSO 68                                        9B     OC.sub.2 H.sub.5                                                                           72    25-70                                                                              DMSO 86                                        10B    OC.sub.2 H.sub.5                                                                           8     40   DMSO 90                                        11B    OC.sub.3 H.sub.7 n                                                                         24    25   DMSO 88                                        12B    OC.sub.3 H.sub.7 iso                                                                       96    25   DMSO 55                                        13B    OC.sub.4 H.sub.9 n                                                                         72    25   DMSO 81                                        14B    OC.sub.8 H.sub.17 -n                                                                       72    25   DMSO 48                                        15B    OCH.sub.2 CH.sub.2 OH                                                                      24    25   DMSO 59                                        16B    OCH.sub.2 CH.sub.2 OCH.sub.3                                                               24    25   DMSO 90                                        17B    OCH.sub.2 CH.sub.2 N(CH.sub.3).sub.2                                                       24    25-45                                                                              DMSO 65                                        __________________________________________________________________________    Example                                                                             MOLECULAR ELEMENTAL ANALYSIS                                            No.   FORMULA          C   H   Cl F  N                                        __________________________________________________________________________    8B    C.sub.16 H.sub.11 ClF.sub.3 NO.sub.5                                                    THEORY 49.31                                                                             2.84                                                                              9.09                                                                             14.63                                                                            3.59                                                     FOUND  49.70                                                                             2.96                                                                              8.85                                                                             14.15                                                                            3.30                                     11B   C.sub.17 H.sub.13 ClF.sub.3 NO.sub.5                                                    THEORY 50.57                                                                             3.24                                                                              8.78                                                                             14.17                                                                            3.47                                                     FOUND  50.85                                                                             3.50                                                                              8.70                                                                             13.70                                                                            3.35                                     12B   C.sub.17 H.sub.13 ClF.sub.3 NO.sub.5                                                    THEORY 50.57                                                                             3.24                                                                              8.78                                                                             14.17                                                                            3.47                                                     FOUND  50.56                                                                             3.26                                                                              8.96                                                                             14.41                                                                            3.41                                     13B   C.sub.18 H.sub.15 ClF.sub.3 NO.sub.5                                                    THEORY 51.75                                                                             3.61                                                                              8.48                                                                             13.64                                                                            3.35                                                     FOUND  51.87                                                                             3.86                                                                              8.47                                                                             13.52                                                                            3.13                                     14B   C.sub.22 H.sub.23 ClF.sub.3 NO.sub.5                                                    THEORY 55.75                                                                             4.88                                                                              7.48                                                                             12.03                                                                            2.97                                                     FOUND  56.14                                                                             5.10                                                                              7.58                                                                             11.48                                                                            2.76                                     15B   C.sub.16 H.sub.11 ClF.sub.3 NO.sub.6                                                    THEORY 47.36                                                                             2.73                                                                              8.73                                                                             14.04                                                                            3.05                                                     FOUND  47.10                                                                             2.72                                                                              8.58                                                                             16.99                                                                            3.29                                     16B   C.sub.16 H.sub.11 ClF.sub.3 NO.sub.6                                                    THEORY 48.64                                                                             3.12                                                                              8.44                                                                             13.57                                                                            3.33                                                     FOUND  48.40                                                                             3.23                                                                              8.68                                                                             13.18                                                                            3.17                                     17B   C.sub.18 H.sub.16 ClF.sub.3 N.sub.2 O.sub.5                                             THEORY 49.95                                                                             3.73                                                                              8.19                                                                             13.17                                                                            6.47                                                     FOUND  48.86                                                                             3.69                                                                              8.14                                                                             13.59                                                                            6.16                                     __________________________________________________________________________

EXAMPLE 18B 5-(2-Chloro-4-trifluoromethylphenoxy)-2-nitrobenzamide

To a 100 ml flask fitted with a magnetic stirrer and drying tube isadded dimethyl sulfoxide (50 ml), anhydrous potassium carbonate (3.6 g,0.026 mole) and 2-chloro-4-trifluoromethylphenol (4.8 L g, 0.024 mole).This mixture is stirred at room temperature overnight.5-Fluoro-2-nitrobenzamide (4.5 g, 0.024 mole) is added rapidly and thereaction mixture stirred at room temperature for 24 hours. The reactionmixture is poured into water (300 ml) and triturated with carbontetrachloride (50 ml). The water and carbon tetrachloride insolublesolid is collected by filtration and dried under vacuum to afford 1.2 gof 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzamide, mp 139°-43°C. Anal. Calcd. for C₁₄ H₈ ClF₃ N₂ O₄ : C, 46.62; H, 2.23; Cl, 9.83; N,7.76. Found: C, 45.77; H, 2.30; Cl, 10.62; N, 7.91.

EXAMPLE 19BN,N-Diethyl-5-(2-Chloro-4-trifluoromethylphenoxy)-2-nitrobenzamide

To a 100 ml flask fitted with a magnetic stirrer and drying tube isadded dimethyl sulfoxide (30 ml), anhydrous potassium carbonate (7.55 g,0.054 mole) and 2-chloro-4-trifluoromethylphenol (10.3 g, 0.052 mole).The mixture is stirred at room temperature overnight. A solution ofN,N-diethyl-5-fluoro-2-nitrobenzamide (12.5 g, 0.052 mole) in dimethylsulfoxide (20 ml) is then added rapidly and the reaction mixture isstirred at room temperature for 60 hours. The reaction mixture is pouredinto water (500 ml) and the product extracted into carbon tetrachloride(4×100 ml), the combined extracts are dried over anhydrous magnesiumsulfate and the solvent removed under vacuum to afford 15.3 g of5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzamide (75% yield)Recrystallization from benzene/hexane affords substantially pure productmp. 75°-79° C. Elemental anal, Calcd. for C₁₈ H₁₆ ClF₃ N₂ O₄ : C, 51.80;H, 3.88; Cl, 8.55; F, 13.68; N, 6.73. Found: C, 52.03; H, 3.90; Cl,8.54; F, 13.59; N, 6.83.

EXAMPLE 20B Methyl 5-(2-Chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate

To a flask fitted with a drying tube is charged DMSO (10 ml),2-chloro-4-trifluoromethylphenol (3.93 g, 0.02 mole) and anhydrouspotassium carbonate (2.76 g, 0.02 mole). Then methyl5-chloro-2-nitrobenzoate (4.3 g, 0.02 mole) is added and the reactionmixture warmed to 50° C. for 3 hours. (Gas-liquid chromatographyanalysis suggested a low conversion to desired product.) The temperatureis raised to 60° C. for 16 hours and then to 70° C. for 16 hours.Additional potassium carbonate (1.38 g, 0.01 mole) is added and heatingat 70° C. is continued for an additional 5 days, the reaction mixture iscooled to room temperature, poured into a benzene/hexane cosolvent andextracted twice with water. The organic layer is dried with anhydroussodium sulfate, filtered and the solvent removed under vacuum (110° C.,0.1 mm) to afford 2.0 g, (27% yield) of methyl5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate which isdetermined by spectral data to be identical with the product of Example1B.

EXAMPLE 21B Methyl 5-(2-Chloro-4-trifluoromethylphenoxy)2-nitrobenzoate

Similarly to Example 20B, tetrahydrothiophene 1,1-dioxide is substitutedfor DMSO and the reaction temperature was maintained at 115° C. for 24hours to afford 2 g of methyl5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate.

EXAMPLE 22B Methyl 5-(2-Chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate

The potassium salt of 2-chloro-4-trifluoromethylphenol is prepared byadding, at 0°-5° C., one equivalent of 2-chloro-4-trifluoromethylphenolto a solution of 1 equivalent of potassium hydroxide dissolved inmethanol. The solvent is removed under vacuum and tetrahydrothiophene1,1-dioxide is added to dissolve the anhydrous potassium salt (II). Thissolution is then added dropwise to 1 equivalent of methyl5-chloro-2-nitrobenzoate dissolved in tetrahydrothioxene 1,1-dioxidepreheated to 105° C. Upon completion of addition the temperature israised to 125° C. for 3 hours, then cooled to room temperature, pouredinto water and extracted into carbon tetrachloride. GLC analysissuggests that the yield is comparable to Example 21B.

By following the general procedures of Examples 1B, 18B, 19B or 20B andselecting the appropriate 4-trifluoromethylphenol (IIa) andhalonitrobenzene (III) there can also be prepared the compounds (I)illustrated in Table V:

                  TABLE V                                                         ______________________________________                                         ##STR22##                                                                     ##STR23##                                                                    Example                                                                       No.    X     X'             m.p. (°C.)                                                                     bp (°C.)/torr                      ______________________________________                                        23B    Cl    OC.sub.2 H.sub.5                                                                             83-84   --                                        24B    Cl                                                                                   ##STR24##     71-72.5 --                                        25B    Cl                                                                                   ##STR25##     oil     180/03                                    26B    Cl                                                                                   ##STR26##     118-20° C.                                                                     --                                        27B    Cl                                                                                   ##STR27##     oil     180/0.3                                   28B    Cl                                                                                   ##STR28##     156-60  --                                        29B    Cl    CH.sub.3       --      135/0.08                                  30B    Cl                                                                                   ##STR29##     oil     180/0.3                                   ______________________________________                                    

The product of Example 28B can also be prepared by acid or basecatalyzed ester hydrolysis of Examples 1B or 8B-17B and the like, oneillustration of which is depicted in Example 31B:

EXAMPLE 31B 5-(2-Chloro-4-trifluoromethylphenoxy)-2-nitrobenzoic acid

Ethyl 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate (Example 8B,20 g., 0.058 mole) is dissolved in ethanol (20 g) and a solution of 50%aqueous sodium hydroxide (9.6 g, 4 g, 0.120 mole) is added dropwisebeginning at 25° C. The rate of addition is adjusted so as to controlthe exothermic reaction at less than or equal to 52° C. By this methodthe sodium salt of 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoicacid is generated in situ. Treatment with 6 M HCl to pH 1 in water (100ml) affords the free acid as a heavy oil which is extracted intoethylene chloride. The ethylene chloride layer is decanted andconcentrated under vacuum to afford 17.6 g of a thick brown syrupymaterial which crystallizes upon further trituration with ethylenedichloride as an off-white powder, mp 156°-60° C. which is identified byspectral means to be5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoic acid.

By standard chemical methods5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoic acid can beconverted to agronomically acceptable alkali and alkaline earth metalsalts by reaction with one equivalent of an appropriate metal hydroxideor to agronomically acceptable amine salts by combining the acid withone equivalent of the appropriate amine. Solutions of the acid salts orfree salts can be obtained depending upon reaction conditions. Onemethod, not meant to be limiting but rather exemplatory, to isolate thesodium salt is described in Example 32B.

EXAMPLE 32B Sodium 5-(2-Chloro-4-trifluoromethylphenoxy)2-nitrobenzoate

5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoic acid (3.0 g, 0.0083mole) is dissolved in iso-propyl alcohol (20 ml) and a solution of 50%aqueous sodium hydroxide (0.644 g, 0.0083 mole) is added dropwise andthe reaction mixture stirred for 1 hour before removing the solvent andwater under vacuum at 0.2 mm overnight to afford 2.8 g of sodium5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate.

EXAMPLE 33B Methyl 5-(4-Chloro-2-trifluoromethylphenoxy)2-nitrobenzoate

To a flask is added DMSO (10 ml) 4-chloro-2-trifluoromethylphenol (3.0g, 0.015 mole), anhydrous potassium carbonate (2-5 g, 70.015 mole) andmethyl 5-fluoro-2-nitrobenzoate (2.99 g, 0.015 mole). The reactionmixture is stirred at room temperature for 7 hours, poured in water (150ml) and then triturated with CCl₄ (50 ml then 35 ml) and the organiclayer decanted and removed under vacuum to afford 5.3 g of product as ayellow oil. Elemental anal. calcd. for C₁₅ H₉ ClF₃ NO₅ : C, 47.90; H,2.42; Cl, 9.68; F, 15.20; N, 3.73. Found: C, 47.70; H, 2.49; Cl, 9.61;F, 14.89; N, 3.31.

What is claimed:
 1. A process for preparing a compound of the formula##STR30## wherein X is hydrogen, halo, trifluoromethyl or lower alkyl;X' is hydrogen, halo, cyano, lower alkyl, lower alkoxy, carboxy,carbalkoxy, carbalkoxyalkoxy, alkoxycarbalkoxy, carbalkenyloxy,carbamoyl, mono- and dialkylcarbamoyl or trifluoromethyl, and X" is haloor trifluoromethyl with the proviso that when X" is halo X istrifluoromethyl, which comprises treating a compound of the formula:##STR31## wherein X and X" are as defined above and X² is fluoro orchloro with an alkali or alkaline earth metal hydroxide at a temperaturein the range of from about 50° to about 100° C. for a period of time inthe range from 5 hour to about 5.5 days in a solvent system comprising adipolar, aprotic solvent having a dielectric constant in the range offrom about 30 to about 70, said solvent being inert or substantiallyinert to said hydroxide, and a non-nucleophilic, hydroxylated cosolventthat increases the solubility of hydroxide to afford atrifluoromethylphenate of the formula ##STR32## wherein X and X" are isas defined above and M is an alkali metal or alkaline earth metalcation, which may be isolated upon acidification as the free phenol orreacted with a halonitrobenzene of the formula: ##STR33## wherein X' isas defined above and halo is fluoro or chloro in a dipolar, apioticsolvent at temperatures ranging from 20°-130° C. for halo being fluoroand from 50°-130° C. for halo being chloro for a period of from one hourto six days depending upon the nature of M, halo, X and X'.
 2. Theprocess of claim 1 for preparing a compound of the formula ##STR34##wherein X and X' are as defined in claim 1 which comprises treating acompound of the formula: ##STR35## wherein X and X² are as defined inclaim 1 with an alkali metal or alkaline metal hydroxide in a solventsystem comprising a non-nucleophilic hydroxy containing solvent and adipolar, aprotic solvent selected from dimethylsulfoxidetetrahydrothiophene-1,1-dioxide or hexamethylphosphoric triamide toafford a compound of the formula ##STR36## wherein X and M are asdefined in claim 1 and then treating said compound with a halobenzene ofthe formula ##STR37## wherein X' is as defined above at a temperature inthe range of from about 20° to 130° C. in a dipolar, aprotic solventselected from dimethyl sulfoxide, dimethylformamide, N-methylacetamide,tetrahydrothiophene 1,1-dioxide, hexamethylphosphoric triamide,1,4-dioxane, ethylene carbonate or 1,2-dimethoxyethane.
 3. The processof claim 2 wherein the non-nucleophilic hydroxy containing compound isselected from among ##STR38## wherein R, R¹, R², R³, R⁴, R⁵, R⁶ and R⁷are the same or different groups selected from hydrogen; straight orbranched lower alkyl, substituted or unsubstituted phenyl substituentswherein phenyl substituents may be alkyl, halo, lower alkoxy, a benzyl,and the like; R⁸ is lower alkyl; n and n² are 0 or 1; n¹ is 0 to 2, n³is an integer of from 1 to 10; n⁴ is 2 to 4 provided that n¹ is 2 onlywhen n and n² are both 0, otherwise the sum of n¹ and n² may notsimultaneously be greater than 1; when n³ is greater than 2, the sum ofn and n² may not simultaneously be greater than 1 and n¹ must be 0; whenR⁷ is hydrogen, n' must be zero and the sum of n and n² must be 1 suchthat at least 3 of the groups R, R' plus either the pair R² and R³ orthe pair of R⁵ and R⁶ must not be hydrogen.
 4. The process of claim 3wherein the hydroxy compound is selected from tert-butanol, pinacol,pentaeythritol, 2,4-dimethyl-2,4-pentanediol, 2,4-dimethyl-2,3,4-pentanetriol, 2,4-dimethyl-3-pentanol, 2,2,2-trimethyl-3-pentanol,2,2-dimethyl-1-propanol, 2,5-dimethyl-3-hexane-2,5-diol,1-methyl-1-cyclohexanol or 2-isopropyl-1-cyclopentanol.
 5. The processof claim 2 wherein the solvents are employed in the ratio of from about1 part to about 30 parts of the non-nulceophilic hydroxy solvent toabout 100 parts of the dipolar, aprotic solvent.
 6. The process of claim5 wherein the solvents are employed in the ratio of from about 5 toabout 20 parts of the non-nucleophilic hydroxy solvent to about 100parts of the dipolar, aprotic solvent.
 7. The process of claim 2 whereinX is chloro, X' is hydrogen, methoxy, ethoxy, carboxy,methoxyethoxycarbonyl, methoxycarbonyl, ethoxycarbonyl,allyloxycarbonyl, sodium carboxylate or potassium carboxylate.
 8. Theprocess of claim 7 wherein X' is sodium carboxylate.
 9. The process ofclaim 7, wherein X' is potassium carboxylate.
 10. The process of claim7, wherein X' is methoxycarbonyl.
 11. The process of claim 7 wherein X'is ethoxycarbonyl.
 12. The process of claim 7 wherein X' ismethoxyethoxycarbonyl.